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Increased CD8+ cytotoxic T cell responses to myelin basic protein in multiple sclerosis
Ying C Q Zang1, Sufang Li, Victor M Rivera
1Multiple Sclerosis Research Unit, Department of Neurology and Baylor Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA. yzang@bcm.tmc.edu
Journal of Immunology (Baltimore, Md. : 1950)
|April 7, 2004
Summary
CD8(+) T cells recognizing myelin basic protein (MBP) peptides are elevated in multiple sclerosis (MS) patients. These T cells show specific cytotoxicity, suggesting a role in MS pathogenesis and oligodendrocyte injury.
Area of Science:
- Immunology
- Neuroscience
- Pathogenesis of Multiple Sclerosis
Background:
- Autoreactive T cells, including CD4(+) and CD8(+) subsets, are implicated in multiple sclerosis (MS) pathogenesis.
- Myelin basic protein (MBP) is a candidate autoantigen in MS.
- CD8(+) T cells play distinct roles in the autoimmune response.
Purpose of the Study:
- To identify MBP-derived peptides with high binding affinity to HLA-A2 and HLA-A24.
- To characterize CD8(+) T cell responses and functional properties in MS patients.
- To investigate the cytotoxic potential of MBP-specific CD8(+) T cells in MS.
Main Methods:
- Identification of MBP-derived peptides binding to HLA-A2 and HLA-A24.
- Characterization of CD8(+) T cell responses using T cell lines and tetramer staining (HLA-A2/MBP(111-119)).
- Assessment of T cell phenotype (Th1, TNF-alpha, IFN-gamma) and cytotoxic activity against target cells.
Main Results:
- Four MBP-derived peptides showed high binding affinity to HLA-A2 and HLA-A24.
- Significantly increased CD8(+) T cell responses to specific MBP peptides (MBP(111-119), MBP(87-95)) were observed in MS patients compared to healthy individuals.
- Generated CD8(+) T cell lines exhibited Th1 phenotype, memory markers, specific cytotoxicity against MBP-pulsed target cells, and lysed MBP-expressing cells.
Conclusions:
- CD8(+) cytotoxic T lymphocytes (CTLs) recognizing MBP are present at increased levels in MS patients.
- These MBP-specific CD8(+) CTLs demonstrate functional cytotoxicity against relevant targets.
- The findings support a role for CD8(+) CTLs targeting MBP in oligodendrocyte injury in MS.